[Influences of tumor necrosis factor-alpha on protein metabolism and cell-cycle kinetics in malignant tumor].

Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma, were injected intraperitoneally with recombinant human TNF-alpha at a dose of 4.75 x 10(6) U/kg for 3 consecutive days. Protein metabolism and cell-cycle kinetics of the tumor were studied. The results showed a significant decrease in tumor volume and weight in comparison with control. TNF resulted in significant decrease in tumor protein fractional synthesis rate (25.3% +/- 3.5%.d-1 versus control 42.9% +/- 2.7%.d-1, P < 0.01), protein synthesis (0.20 +/- 0.05 g/d versus control 1.14 +/- 0.20 g/d, P < 0.001) and fractional growth rate (24.3% +/- 2.1%.d-1 versus control 35.8% +/- 2.3%.d-1, P < 0.01), but no change of tumor protein fractional degradation rate. TNF also resulted in remarkable decline in labelling index (30.8% +/- 4.2% versus control 44.7% +/- 4.2%, P < 0.01) and G1 phase increase (6.0% +/- 1.3% versus control 12.2% +/- 2.5%, P < 0.01) of tumor cells, 6 hours after injection of bromodeoxyuridine, by flow cytometry. The results indicate that TNF inhibits tumor growth as a result of decreases in tumor cell DNA and protein syntheses.